The pyruvate kinase M (PKM) gene can be alternatively spliced to form either PKM1, which is expressed in most adult tissues, or PKM2, which is expressed in embryonic cells and also tumour cells. The splicing of PKM is regulated by the expression of three heterogeneous nuclear ribonucleoprotein (hnRNP) splicing repressors, hnRNPA1, hnRNPA2 and polypyrimidine tract-binding protein 1 (PTB). However, the mechanism by which these hnRNPs determine the expression of PKM1 or PKM2 has remained unclear. Chen and colleagues characterized the binding of these hnRNPs to PKM and found that the sites bound by these splicing repressors changed according to their expression level. As MYC upregulates the expression of these hnRNPs, which favours the expression of the PKM2 isoform, this paper uncovers how PKM2, rather than PKM1, might be induced in tumour cells.
ORIGINAL RESEARCH PAPER
Chen, M. et al. Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nature Struct. Mol. Biol. 5 Feb 2012 (doi:10.1038/nsmb.2219)
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Alderton, G. Dose-dependent splicing. Nat Rev Cancer 12, 153 (2012). https://doi.org/10.1038/nrc3241
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DOI: https://doi.org/10.1038/nrc3241